The Neuropathology Core was established during the first five years of the Huntington's Disease Center without Walls and has continued to serve the Center during years 06-20. Our initial mission was to promote brain donation for research, to examine the brains obtained and to distribute tissue to the Center's investigators. However, we have developed expanded procedures to enhance the value of the collected brains to investigators whose specific research projects depend upon receiving carefully prepared and examined tissue. The specific aims of the Neuropathology Core are: 1) To establish an accurate diagnosis on all brains submitted to the Center; 2) To prepare samples according to protocols that lead to standardized tissue preparation for research; 3) To organize the availability, storage and distribution of tissue samples from HD patients and from controls; 4) To build a library of paraffin embedded tissue of precise brain areas from patients with HD or with basal ganglia degeneration other than HD, and from controls for further investigations and comparisons; and 5) To apply 'in situ' hybridization (ISH) and immunoperoxidase methods for projects in the Core Laboratory. To achieve these goals, the Core includes individuals with expertise in neuropathology, morphometry, immunocytochemistry, ISH and Brain Banking. Full characterization of brains is critical to obtain maximal information from them and to enhance the value of the tissue for research. Brains are processed using methods that permit accurate diagnoses while still meeting the needs for investigators, ensuring complete and reproducible examinations across all specimens collected. The Core also assists investigators in evaluating tissue sections from human brains or animal models in comparing histologic features as revealed by conventional and specific methods and in correlating the features observed in the animal models with those recorded in human brains. The unique neuropathology of Huntington disease (HD) dictate that investigators must ultimately rely on HD human tissue to unveil its pathogenesis. Thus, in the grant renewal period, Core B will provide essential tissue and services for all projects in the HD Center.